TAL1/SCL Is Expressed in Endothelial Progenitor Cells/Angioblasts and Defines a Dorsal-to-Ventral Gradient of Vasculogenesis

Drake, Christopher J.; Brandt, Stephen J.; Trusk, Thomas C.; Little, Charles D.

doi:10.1006/dbio.1997.8751

Cited by 158 publications

(138 citation statements)

References 43 publications

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“…3). These data are consistent with the highly conserved pattern of SCL expression previously reported in zebrafish (2,3,6) and in higher vertebrates (5,6,53). Although kidney and spleen are the main hemopoietic organs in fish, hemopoiesis has also been reported in both liver and heart (30), and the gills are rich in endothelial cells.…”

Section: Resultssupporting

confidence: 92%

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Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Barton

Göttgens

Gering

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The stem cell leukemia (SCL) gene encodes a tissue-specific basic helix-loop-helix (bHLH) protein with a pivotal role in hemopoiesis and vasculogenesis. Several enhancers have been identified within the murine SCL locus that direct reporter gene expression to subdomains of the normal SCL expression pattern, and long-range sequence comparisons of the human and murine SCL loci have identified additional candidate enhancers. To facilitate the characterization of regulatory elements, we have sequenced and analyzed 33 kb of the SCL genomic locus from the pufferfish Fugu rubripes, a species with a highly compact genome. Although the pattern of SCL expression is highly conserved from mammals to teleost fish, the genes flanking pufferfish SCL were unrelated to those known to flank both avian and mammalian SCL genes. These data suggest that SCL regulatory elements are confined to the region between the upstream and downstream flanking genes, a region of 65 kb in human and 8.5 kb in pufferfish. Consistent with this hypothesis, the entire 33-kb pufferfish SCL locus directed appropriate expression to hemopoietic and neural tissue in transgenic zebrafish embryos, as did a 10.4-kb fragment containing the SCL gene and extending to the 5 and 3 flanking genes. These results demonstrate the power of combining the compact genome of the pufferfish with the advantages that zebrafish provide for studies of gene regulation during development. Furthermore, the pufferfish SCL locus provides a powerful tool for the manipulation of hemopoiesis and vasculogenesis in vivo.T he stem cell leukemia (SCL) gene (also known as Tal-1) encodes a basic helix-loop-helix (bHLH) transcription factor that is a critical regulator of both hemopoiesis and vasculogenesis (1). SCL is normally expressed in hemopoietic stem cells, in committed cells of the erythroid, myeloid, and megakaryocytic lineages, in endothelium, and within specific regions of the central nervous system, a pattern of expression that is highly conserved across vertebrate species from mammals to teleost fish (2-6).SCL is essential for the development of all hemopoietic lineages (7,8). A role in early progenitors is also suggested by the observation that expression of anti-sense SCL suppressed the proliferation, cell cycle progression, and self renewal of a multipotent hemopoietic cell line (9). Distinct functions following lineage commitment are implied by the modulation of SCL mRNA and protein levels during erythroid and myeloid differentiation (10-14). Moreover, enforced SCL expression enhanced erythroid differentiation of hemopoietic cell lines (14, 15) and increased erythroid and megakaryocytic differentiation of normal CD34-positive progenitors (16,17).SCL also plays a crucial role in the formation of hemangioblasts, bipotent progenitors of both blood and endothelium. Ectopic expression of SCL mRNA in zebrafish embryos specifies hemangioblast formation from early mesoderm and results in excessive production of blood and endothelial progenitors (3). In keeping with this, SCL can parti...

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Section: Resultssupporting

confidence: 92%

“…SCL is normally expressed in hemopoietic stem cells, in committed cells of the erythroid, myeloid, and megakaryocytic lineages, in endothelium, and within specific regions of the central nervous system, a pattern of expression that is highly conserved across vertebrate species from mammals to teleost fish (2)(3)(4)(5)(6).…”

mentioning

confidence: 99%

Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Barton

Göttgens

Gering

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…During angiogenesis, proliferating ECs organize to form new three-dimensional capillary networks through a process involving transition of endothelial precursor cells to a spindle-shape morphology (32) in combination with alignment into solid, multicellular, precapillary, cord-like structures (33). Moreover, these cord-like structures are interconnected to form a polygonal network (32,34).…”

Section: Resultsmentioning

confidence: 99%

Rho activity critically and selectively regulates endothelial cell organization during angiogenesis

Hoang

Whelan

Senger

2004

Proc. Natl. Acad. Sci. U.S.A.

179

187

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The mechanisms that control organization of endothelial cells (ECs) into new blood vessels are poorly understood. We hypothesized that the GTPase Rho, which regulates cytoskeletal architecture, is important for EC organization during neovascularization. To test this hypothesis, we designed a highly versatile mouse skin model that used vascular endothelial growth factor-expressing cells together with packaging cells producing retroviruses encoding RhoA GTPase mutants. In this animal model, dominant negative N19RhoA selectively impaired assembly of ECs into new blood vessels; and, in contrast, active V14RhoA stimulated ECs to form blood vessels with functional lumens. In vitro, dominant negative N19RhoA reduced EC actin stress fibers and prevented ECs from contracting and reorganizing into precapillary cords within collagen gels. In contrast, active V14RhoA promoted EC stress fiber formation, contractility, and organization into cords. Neither N19RhoA nor V14RhoA significantly affected EC proliferation or migration in vitro; and, similarly, neither mutant significantly affected EC density during angiogenesis in vivo. Thus, these studies identify a critical and selective role for Rho activity in regulating EC assembly into new blood vessels, and they identify both negative and positive manipulation of Rho activity, respectively, as strategies for suppressing or promoting the organizational stages of neovascularization.

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“…VEGF is generally considered to regulate vascular differentiation and morphogenesis via VEGFR-2, although it is not clear if it is indispensable for angioblastic specification and differentiation (Vokes and Krieg, 2002). This endothelial differentiation process is mediated by the transcription factor SCL/TAL (expressed in the subepicardium) (Pérez-Pomares et al, unpublished results), which is known to be essential in the angioblastic splanchnopleural differentiation (Drake et al, 1997;Drake and Flemming, 2000) as well as in the specification of hematopoietic cells (Robb et al, 1995;Begley and Green 1999).…”

Section: The Fate Of the Epdc Epdcs And Coronary Endotheliummentioning

confidence: 99%

The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells

2003

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After its initial formation the epicardium forms the outermost cell layer of the heart. As a result of an epithelial-to-mesenchymal transformation (EMT) individual cells delaminate from this primitive epicardial epithelium and migrate into the subepicardial space (Pérez-Pomares et al., Dev Dyn 1997; 210: 96 -105; Histochem J 1998a;30:627-634 Dev. Biol. 2002b;247:307-326). A subset of EPDCs continue to differentiate in a variety of different cell types (including coronary endothelium, coronary smooth muscle cells (CoSMCs), interstitial fibroblasts, and atrioventricular cushion mesenchymal cells), whereas other EPDCs remain in a more or less undifferentiated state. Based on its specific characteristics, we consider the EPDC as the ultimate 'cardiac stem cell'. In this review we briefly summarize what is known about events that relate to EPDC development and differentiation while at the same time identifying some of the directions where EPDCrelated research might lead us in the near future. Anat Rec Part A 276A: 43-57, 2004.

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TAL1/SCL Is Expressed in Endothelial Progenitor Cells/Angioblasts and Defines a Dorsal-to-Ventral Gradient of Vasculogenesis

Cited by 158 publications

References 43 publications

Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Rho activity critically and selectively regulates endothelial cell organization during angiogenesis

The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells

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